Identification of candidate microRNAs associated with tuberculosis in Thai cynomolgus macaques (Macaca fascicularis)

Abstract

Background: Cynomolgus macaques frequently inhabit areas close to human populations, increasing the risk of Mycobacterium tuberculosis complex (MTBC) transmission between humans and non-human primates (NHPs). Tuberculosis (TB) is a chronic airborne disease caused by MTBC, leading to high mortality in humans and NHPs. Controlling TB transmission within and between these species remains a significant challenge due to the complexities of diagnosing TB in NHPs, which necessitate the use of multiple diagnostic tools to ensure accurate and sensitive detection. Emerging evidence suggests that microRNAs (miRNAs) exhibit distinct expression patterns in MTBC infection, making them promising biomarkers for disease detection and monitoring.

Objective: This study aimed to identify candidate miRNA biomarkers associated with active tuberculosis in cynomolgus macaques.

Methods: The plasma samples of cynomolgus macaques were obtained from Krabok-Koo Wildlife Rescue Center, Chachoengsao, Thailand. Eight monkeys were selected and divided into 2 groups, including active TB (n = 4) and uninfected TB (n = 4). The extracted miRNAs were constructed for cDNA libraries and single-end (50 cycles) sequenced in duplicate by DNBSEQ-G400 platform (MGI, China). The data analysis was performed using miRdeep2 and DESeq2 pipelines to identify candidate miRNA biomarkers.

Results: Interestingly, there were 10 miRNAs with significant differential expression in active TB compared to uninfected TB including 5 upregulated and 5 downregulated miRNAs. Five upregulated miRNAs might serve as candidate biomarkers, including miR-200c-5p, miR-664, miR-1262-5p, miR-580, and miR-760.

Conclusion: This study identified a panel of differentially expressed miRNAs as candidate biomarkers for TB infection in cynomolgus macaques, suggesting their potential role in TB pathogenesis.